The proposed studies will: 1. Determine the mechanisms regulating cyclin D1 transcription and activity by transactivators/co-regulators using cultured cells, inducible lines, and transgenic mice, and identify the target DNA sequence required for regulation of the cycin D1 gene. 2. The requirement for cyclin D1 transformation by Neu and b-catenin/APC will be evaluated using anti-sense techniques, transgenic and knockout mice. The requirement for cyclin D1 in b-catenin/APC induced tumorigenesis will be determined. The requirement for c-Jun/cyclin D1 in mammary oncogenesis will be tested using inducible knockout gene technology.